Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36093   clinical trials with a EudraCT protocol, of which   5934   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Phase III clinical trial to evaluate the efficacy and safety of chondroitin sulphate and glucosamine sulphate in combination versus placebo in patients with osteoarthritis of the knee.

    Summary
    EudraCT number
    2013-000444-26
    Trial protocol
    ES  
    Global end of trial date
    21 Aug 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Mar 2016
    First version publication date
    13 Mar 2016
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    TM-CS+SG/301
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01893905
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Tedec-Meiji Farma, S.A.
    Sponsor organisation address
    Ctra. M-300, Km. 30,500, Alcalá de Henares (Madrid), Spain, 28802
    Public contact
    Departamento Investigación Clínica, Tedec-Meiji Farma, S.A., 34 918870980, m.gimeno@tedecmeiji.com
    Scientific contact
    Departamento Investigación Clínica, Tedec-Meiji Farma, S.A., 34 918870980, m.gimeno@tedecmeiji.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Sep 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Aug 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of the combination of chondroitin sulphate + glucosamine sulphate (CS+SG) manufactured by Tedec-Meiji Farma, S.A. compared to placebo in patients with osteoarthritis of the knee.
    Protection of trial subjects
    Acetaminophen upon demand, maximum 4g/day, was allowed for pain relief if necessary. Any other rescue medication considered necessary for any pathology during the study, was administered based on investigator judgment based on the clinical condition of the patient
    Background therapy
    Acetaminophen upon demand, maximum 4g/day, as rescue medication.
    Evidence for comparator
    According to EMA Guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis, if a drug is intended to be approved for pain relief, a placebo-controlled design is recommended. In addition, the comparator choice was proposed by the Spanish Agency for Medicines and Medical Devices(AEMPS).
    Actual start date of recruitment
    15 May 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 158
    Worldwide total number of subjects
    158
    EEA total number of subjects
    158
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    58
    From 65 to 84 years
    100
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Recruitment started in June 2013 and the last follow-up was performed on August 2014. This study enrolled patients from the Rheumatology and Traumatology Departments belonging to 10 centres located in Spain.

    Pre-assignment
    Screening details
    A total of 193 patients were screened, of whom 29 (15%) were screening failures. At the screening visit, the patients were assessed by the blinded physician for fulfilment of the selection criteria, demographic characteristics and medical history. Knee radiographs were also obtained.

    Pre-assignment period milestones
    Number of subjects started
    158
    Number of subjects completed
    158

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor
    Blinding implementation details
    Test and control treatments were presented in the form of sachets with powder to be dissolved in water. External appearance of the sachets from the two groups was the same, in order to make both treatments indistinguishable. The trial medication was packaged and labelled separately for each patient. It contained the corresponding randomisation number according to a list previously generated and with no identification of the treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Placebo of chondrotin sulfate + glucosamine sulfate orally administered once a day for 24 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Powder for oral solution (sachets). One sachet was administered once daily during a period of 24 weeks.

    Arm title
    CS+SG
    Arm description
    Chondrotin sulfate + glucosamine sulfate orally administered once a day for 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Chondroitin sulfate 1200mg + glucosamine sulfate 1500mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Powder for oral solution (sachets). One sachet was administered once daily during a period of 24 weeks.

    Number of subjects in period 1
    Placebo CS+SG
    Started
    78
    80
    Completed
    64
    55
    Not completed
    14
    25
         Protocol deviation
    1
    6
         Other
    3
    1
         Lack of adherrence to treatment
    -
    2
         Lack of efficacy
    7
    5
         Adverse event, non-fatal
    3
    9
         Consent withdrawn by subject
    -
    1
         Lost to follow-up
    -
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo of chondrotin sulfate + glucosamine sulfate orally administered once a day for 24 weeks.

    Reporting group title
    CS+SG
    Reporting group description
    Chondrotin sulfate + glucosamine sulfate orally administered once a day for 24 weeks.

    Reporting group values
    Placebo CS+SG Total
    Number of subjects
    78 80 158
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    67.6 ± 8.9 65.49 ± 8.17 -
    Gender categorical
    Units: Subjects
        Female
    67 65 132
        Male
    11 15 26
    Race/ethnicitiy
    Units: Subjects
        Caucasian
    77 79 156
        Other
    1 1 2
    Body Mass Index
    Units: kg/m^2
        arithmetic mean (standard deviation)
    27.99 ± 3.26 28.56 ± 3.49 -
    Time to first osteoarthritis symptoms
    Units: Years
        arithmetic mean (standard deviation)
    6.12 ± 5.2 6.35 ± 5.91 -
    Mean global pain on VAS
    Units: cm
        arithmetic mean (standard deviation)
    62.05 ± 11.77 62.15 ± 11 -
    WOMAC global on VAS
    Units: cm
        arithmetic mean (standard deviation)
    52.37 ± 14.53 52.69 ± 12 -
    WOMAC pain on VAS
    Units: cm
        arithmetic mean (standard deviation)
    53.38 ± 14.37 52.76 ± 12.5 -
    WOMAC stiffness on VAS
    Units: cm
        arithmetic mean (standard deviation)
    52.28 ± 17.53 49.71 ± 16.45 -
    WOMAC function on VAS
    Units: cm
        arithmetic mean (standard deviation)
    52.08 ± 15.56 53.02 ± 12.85 -
    Patient's Global Assessment on VAS
    Units: cm
        arithmetic mean (standard deviation)
    59.91 ± 14.05 63.45 ± 13.67 -
    Investigator's Global Assessment on VAS
    Units: cm
        arithmetic mean (standard deviation)
    57.35 ± 14.37 57.06 ± 11.87 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo of chondrotin sulfate + glucosamine sulfate orally administered once a day for 24 weeks.

    Reporting group title
    CS+SG
    Reporting group description
    Chondrotin sulfate + glucosamine sulfate orally administered once a day for 24 weeks.

    Primary: Absolute Change in Global Pain Reduction (VAS) at the End of Follow-up

    Close Top of page
    End point title
    Absolute Change in Global Pain Reduction (VAS) at the End of Follow-up
    End point description
    Global Pain was assessed two times in each visit using the VAS (visual analogue scale) for which 0=no pain and 100=worst pain imaginable. Reduction of Global Pain according to VAS is defined in absolute and relative terms as follows: - Absolute change in Global Pain at the end of treatment is calculated as the difference between the Global Pain reported in the last visit and the baseline visit. A negative change indicates a reduction in Global Pain, while a positive change indicates an increment in Global Pain. - Relative change in Global Pain at the end of treatment is calculated as the percentual change between the Global Pain reported in the last visit and the baseline visit. A negative change indicates a reduction in Global Pain, while a positive change indicates an increment in Global Pain.
    End point type
    Primary
    End point timeframe
    24 weeks
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: cm
        arithmetic mean (standard deviation)
    -20.57 ± 2.41
    -11.86 ± 2.42
    Statistical analysis title
    Statistical Analysis Primary Endpoint
    Statistical analysis description
    Analysis was performed based on the modified intention-to-treat population. The imputation method for handling missing data was MMRM. The alpha error adjustment and sample size necessary to conduct the interim analysis were estimated according to Pocock approach.
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0314
    Method
    Mixed models analysis
    Confidence interval

    Primary: Relative Change in Global Pain Reduction (VAS) at the End of Follow-up

    Close Top of page
    End point title
    Relative Change in Global Pain Reduction (VAS) at the End of Follow-up
    End point description
    Global Pain was assessed two times in each visit using the VAS (visual analogue scale) for which 0=no pain and 100=worst pain imaginable. Reduction of Global Pain according to VAS is defined in absolute and relative terms as follows: - Absolute change in Global Pain at the end of treatment is calculated as the difference between the Global Pain reported in the last visit and the baseline visit. A negative change indicates a reduction in Global Pain, while a positive change indicates an increment in Global Pain. - Relative change in Global Pain at the end of treatment is calculated as the percentual change between the Global Pain reported in the last visit and the baseline visit. A negative change indicates a reduction in Global Pain, while a positive change indicates an increment in Global Pain.
    End point type
    Primary
    End point timeframe
    24 weeks
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: Percentage of change
        arithmetic mean (standard deviation)
    -33.16 ± 3.98
    -18.9 ± 3.99
    Statistical analysis title
    Statistical Analysis Primary Endpoint
    Statistical analysis description
    Analysis was performed based on the modified intention-to-treat population. The imputation method for handling missing data was MMRM. The alpha error adjustment and sample size necessary to conduct the interim analysis were estimated according to Pocock approach.
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0475
    Method
    Mixed models analysis
    Confidence interval

    Secondary: Responders OMERACT-OARSI 2004 at the End of Follow-up

    Close Top of page
    End point title
    Responders OMERACT-OARSI 2004 at the End of Follow-up
    End point description
    Percentage of subjects with a clinical response according to Osteaorthritis Research Society International (OARSI) 2004 criteria at the end of follow-up. Patients were classified as responders if the pain or physical function score decreased at least 50% and at least 20mm on the Visual Analogue Scale, or if two of the following three findings were recorded: a decrease in pain of at least 20% or at least 10mm on the VAS, a decrease in physical function of at least 20% and at least 10mm on the VAS, or an increase in the score of the patient's global assessment by at least 20% and at least 10mm on the VAS.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: Percentage of responders
        number (not applicable)
    56.41
    50
    Statistical analysis title
    Statistical Analysis Secondary Endpoint
    Statistical analysis description
    Analysis was performed based on the modified intention-to-treat population. The imputation method for handling missing data was MMRM. The alpha error adjustment and sample size necessary to conduct the interim analysis were estimated according to Pocock approach.
    Comparison groups
    CS+SG v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4195
    Method
    Chi-squared
    Confidence interval

    Secondary: WOMAC Global (VAS) at the End of Follow-up

    Close Top of page
    End point title
    WOMAC Global (VAS) at the End of Follow-up
    End point description
    The WOMAC measures include 5 items for pain intensity, 2 for joint stiffness, and 17 for physical function. These items are measured on a 0-100 VAS for which 0=none and 100=the worst pain intensity/joint stiffness/functional impairment respectively.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: cm
        arithmetic mean (standard deviation)
    37.37 ± 2.06
    43.27 ± 2.06
    Statistical analysis title
    Statistical Analysis Secondary Endpoint
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0472
    Method
    Mixed models analysis
    Confidence interval

    Secondary: WOMAC Pain (VAS) at the End of Follow-up

    Close Top of page
    End point title
    WOMAC Pain (VAS) at the End of Follow-up
    End point description
    The WOMAC measures include 5 items for pain intensity, 2 for joint stiffness, and 17 for physical function. These items are measured on a 0-100 VAS for which 0=none and 100=the worst pain intensity/joint stiffness/functional impairment respectively.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: cm
        arithmetic mean (standard deviation)
    37.42 ± 2.22
    44.31 ± 2.23
    Statistical analysis title
    Statistical Analysis Secondary Endpoint
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0443
    Method
    Mixed models analysis
    Confidence interval

    Secondary: WOMAC Stiffness (VAS) at the End of Follow-up

    Close Top of page
    End point title
    WOMAC Stiffness (VAS) at the End of Follow-up
    End point description
    The WOMAC measures include 5 items for pain intensity, 2 for joint stiffness, and 17 for physical function. These items are measured on a 0-100 VAS for which 0=none and 100=the worst pain intensity/joint stiffness/functional impairment respectively.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: cm
        arithmetic mean (standard deviation)
    34.51 ± 2.49
    42.23 ± 2.5
    Statistical analysis title
    Statistical Analysis Secondary Endpoint
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0231
    Method
    Mixed models analysis
    Confidence interval

    Secondary: WOMAC Function (VAS) at the End of Follow-up

    Close Top of page
    End point title
    WOMAC Function (VAS) at the End of Follow-up
    End point description
    The WOMAC measures include 5 items for pain intensity, 2 for joint stiffness, and 17 for physical function. These items are measured on a 0-100 VAS for which 0=none and 100=the worst pain intensity/joint stiffness/functional impairment respectively.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: cm
        arithmetic mean (standard deviation)
    37.74 ± 2.06
    43.07 ± 2.07
    Statistical analysis title
    Statistical Analysis Secondary Endpoint
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0683
    Method
    Mixed models analysis
    Confidence interval

    Secondary: Investigator's Global Assessment (VAS) at the End of Follow-up

    Close Top of page
    End point title
    Investigator's Global Assessment (VAS) at the End of Follow-up
    End point description
    The WOMAC measures include 5 items for pain intensity, 2 for joint stiffness, and 17 for physical function. These items are measured on a 0-100 VAS for which 0=none and 100=the worst pain intensity/joint stiffness/functional impairment respectively.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: cm
        arithmetic mean (standard deviation)
    35.54 ± 2.12
    42.11 ± 2.12
    Statistical analysis title
    Statistical Analysis Secondary Endpoint
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0391
    Method
    Mixed models analysis
    Confidence interval

    Secondary: Patient's Global Assessment (VAS) at the End of Follow-up

    Close Top of page
    End point title
    Patient's Global Assessment (VAS) at the End of Follow-up
    End point description
    The WOMAC measures include 5 items for pain intensity, 2 for joint stiffness, and 17 for physical function. These items are measured on a 0-100 VAS for which 0=none and 100=the worst pain intensity/joint stiffness/functional impairment respectively.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: cm
        arithmetic mean (standard deviation)
    41.38 ± 2.4
    46.21 ± 2.41
    Statistical analysis title
    Statistical Analysis Secondary Endpoint
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1163
    Method
    Mixed models analysis
    Confidence interval

    Secondary: Consumption of Rescue Medication for Osteroarthritis Pain

    Close Top of page
    End point title
    Consumption of Rescue Medication for Osteroarthritis Pain
    End point description
    Consumption of rescue medication for osteoarthritis throughout the study.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    78
    80
    Units: percentage of patients
        number (not applicable)
    92.31
    90
    Statistical analysis title
    Consumption of Rescue Medication for Pain
    Statistical analysis description
    Analysis was performed based on the modified intention-to-treat population. The imputation method for handling missing data was MMRM. The alpha error adjustment and sample size necessary to conduct the interim analysis were estimated according to Pocock approach.
    Comparison groups
    CS+SG v Placebo
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.6098
    Method
    Chi-squared
    Confidence interval

    Secondary: Mean Daily Dose of Paracetamol Consumption

    Close Top of page
    End point title
    Mean Daily Dose of Paracetamol Consumption
    End point description
    Mean daily dose of paracetamol consumption throughout the study.
    End point type
    Secondary
    End point timeframe
    Throughout the study.
    End point values
    Placebo CS+SG
    Number of subjects analysed
    72
    69
    Units: g/day
        arithmetic mean (standard deviation)
    0.77 ± 0.68
    0.65 ± 0.53
    Statistical analysis title
    Mean Daily Dose of Paracetamol Consumption
    Statistical analysis description
    Analysis was performed based on the modified intention-to-treat population. The imputation method for handling missing data was MMRM. The alpha error adjustment and sample size necessary to conduct the interim analysis were estimated according to Pocock approach.
    Comparison groups
    Placebo v CS+SG
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5038
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    24 weeks.
    Adverse event reporting additional description
    All those patients who have received at least 1 administration of the study product or placebo were included in the safety analysis. Throughout the study, all adverse events were recorded in the Case Report Form. Adverse events recording, physical examination and analytical parameters were considered as safety variables.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Placebo Group
    Reporting group description
    Placebo group.

    Reporting group title
    CS+SG group
    Reporting group description
    -

    Serious adverse events
    Placebo Group CS+SG group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 80 (2.50%)
    2 / 80 (2.50%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 80 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 80 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Placebo Group CS+SG group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 80 (23.75%)
    33 / 80 (41.25%)
    Investigations
    Decreased appetite
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 80 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 80 (1.25%)
         occurrences all number
    1
    1
    Headache
         subjects affected / exposed
    3 / 80 (3.75%)
    10 / 80 (12.50%)
         occurrences all number
    3
    10
    Somnolence
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Eye disorders
    Eye pruritus
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 80 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 80 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    2
    Influenza like illness
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 80 (1.25%)
         occurrences all number
    1
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 80 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    3
    Constipation
         subjects affected / exposed
    2 / 80 (2.50%)
    2 / 80 (2.50%)
         occurrences all number
    2
    3
    Diarrhoea
         subjects affected / exposed
    1 / 80 (1.25%)
    3 / 80 (3.75%)
         occurrences all number
    1
    3
    Flatulence
         subjects affected / exposed
    1 / 80 (1.25%)
    4 / 80 (5.00%)
         occurrences all number
    1
    4
    Nausea
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    2 / 80 (2.50%)
    2 / 80 (2.50%)
         occurrences all number
    2
    2
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    2 / 80 (2.50%)
    2 / 80 (2.50%)
         occurrences all number
    2
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Muscle spasms
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Muscular weakness
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    2 / 80 (2.50%)
    3 / 80 (3.75%)
         occurrences all number
    2
    3
    Infections and infestations
    Cystitis
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 80 (1.25%)
         occurrences all number
    1
    1
    Diarrhoea infectious
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    2 / 80 (2.50%)
    2 / 80 (2.50%)
         occurrences all number
    2
    2
    Laryngitis
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    6 / 80 (7.50%)
    1 / 80 (1.25%)
         occurrences all number
    6
    1
    Pharyngitis
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 80 (1.25%)
         occurrences all number
    2
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 May 2013
    Inclusion of a new site: Hospital Universitario Fundación Alcorcón (Madrid) and Dr Gavín González as Principal Investigator.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None.
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA